Chronic Glucocorticoid Use Research Articles

8248 Glucocorticoid Induced Adrenal Crisis Masked By Metastatic Lung Carcinoma

Abstract Disclosure: N. Abrahimi: None. A. Abrahimi: None. Background: Chronic glucocorticoid use of three weeks or longer can cause hypothalamic-pituitary-adrenal axis inhibition by negative feedback, causing adrenal suppression. (1) Adrenal crisis is diagnosed by an acute clinical decompensation, persistent hypotension that resolves with high dose steroid administration. (2) Adrenal crisis is precipitated by several causes such as illness, dehydration, trauma, emotional distress and sometimes due to no identifiable cause. (2) Clinical Case: 64-year-old male past medical history of lung carcinoma metastatic to mediastinum who presented to the hospital with tachycardia. On presentation, patient was tachycardic, tachypneic, and hypotensive. Labs significant for WBC 22, Na+ 129, K+ 3.2, Cr 3.4. Patient received 2.5 L bolus of NS and was given one dose of azithromycin due to concern for sepsis. After fluid resuscitation, hypotension and tachycardia resolved. Presenting symptoms included ongoing nausea, decreased appetite and malaise for several weeks. Repeat labs post fluid resuscitation showed resolution of leukocytosis, improvement of AKI, and repletion of electrolytes. CT chest abdomen pelvis showed questionable pneumonia, however, consolidations were difficult to distinguish from known malignant masses. Clinical picture was not consistent with pneumonia and so additional antibiotics were held. Several hours later, blood pressure decreased, and patient began requiring vasopressors. Cefepime was started given concern for septic shock. Nearly 48 hours after initiation of broad-spectrum antibiotics hypotension persisted and patient remained on vasopressors. Given clinical decline, etiology of shock was reconsidered. Patient reported daily prednisone use over the last several months for COPD management. Given high clinical suspicion of adrenal crisis in setting of chronic steroid use and glucocorticoid withdrawal, patient was started on hydrocortisone 100 mg every 8 hours. Shortly after initiation of stress dosed steroids, the patient was successfully weaned off vasopressors with complete resolution of hypotension. Conclusion: Presentation and symptoms of adrenal insufficiency and crisis including nausea, anorexia, fatigue, malaise, hypotension and electrolyte abnormalities are nonspecific, can go unrecognized and be masked by other disease processes, such as metastatic cancer. (1) Adrenal crisis is life threatening and must be diagnosed and treated early to prevent mortality. (2) Therefore, adrenal crisis should always be on the differential in patients who present with shock.

6722 Increase in Femoral Neck BMD After Parathyroidectomy in Patients with Mild Primary Hyperparathyroidism

Abstract Disclosure: F. Abdul Kather: None. G.A. Clines: None. C. Janney: None. D.T. Hughes: None. N.H. Esfandiari: None. S. Saberi: None. Objective: This study aimed to assess changes in bone mineral density (BMD) following parathyroidectomy in patients with mild primary hyperparathyroidism, defined as serum calcium 10.4 mg/dl to 11.2 mg/dl, by comparing distinct patient variables. Hypothesis: Pre-op demographic factors, laboratory values, and BMD significantly influence post-parathyroidectomy BMD. Methods: This retrospective chart review included 93 subjects with primary hyperparathyroidism who underwent parathyroidectomy between 2000-2022 with BMD measurements performed at the same site pre- and post-parathyroidectomy. Exclusion criteria were age <50 years, GFR <30, recurrent primary hyperparathyroidism, chronic oral glucocorticoid use (>1 month), rheumatoid arthritis, suppressed serum TSH, hormone-deprivation therapy, cinacalcet use, and prescription osteoporosis medication therapy. Statistical analyses were performed using ANOVA and a p-value of <0.05 was considered statistically significant. Results: The mean age of the subjects was 63.65 ± 6.58 years, who were mostly female (84.9%) and white (88.2%). Pre-op laboratory values revealed mean uncorrected calcium 10.52 ±0.26 mg/dL, corrected calcium 10.25 ± 0.32 mg/dL, 25-OH vitamin D 35.82 ±15.31 ng/mL, and parathyroid hormone (PTH) 99.12 ±37.06 pg/mL. Pre-op mean bone densities for the lumbar spine, femoral neck, and total hip were 1.04 ± 0.16, 0.81 ± 0.11, and 0.87 ± 0.11 g/cm2, respectively, with corresponding T-scores of -1.13 ± 1.23, -1.60 ± 0.74, and -1.13 ± 0.89. Changes in BMD post-parathyroidectomy were determined by comparing pre-op and post-op DXA scans. No statistically significant differences in DXA were found between ages of 50-55 vs. >55, post-op timing of DXA 1-2 years post parathyroidectomy vs. >2 years post parathyroidectomy, number of parathyroid glands removed, the total weight of resected parathyroid glands, pre-op vitamin D level <30 ng/mL vs. ≥30 ng/mL, or pre-op urinary calcium levels <200 mg/day vs. ≥200 mg/day. Grouping subjects by pre-operative DXA T-scores revealed a statistically significant improvement in femoral neck bone density between osteoporotic and osteopenic subjects (p=0.018) and between osteoporotic and normal bone density subjects (p=0.019). No significant differences were identified in the spine and total hip bone density changes among these groups. Conclusion: In subjects with osteoporosis undergoing parathyroidectomy, a significant improvement in femoral neck bone density was observed, unaffected by pre-op variables of age, timing of DXA post parathyroidectomy, parathyroid gland characteristics, and pre-op vitamin D and urinary calcium levels. These findings underscore the potential for tailored interventions in managing bone health post-parathyroid surgery, emphasizing the need for personalized approaches to optimize outcomes in individuals with mild hyperparathyroidism. Presentation: 6/2/2024

7627 Prevalence Of True Endocrinopathies In Patients Presenting To An Endocrine Clinic With Fatigue

Abstract Disclosure: C. Dimech: None. K. Barnett: None. F. Hasan: None. Introduction: Fatigue is a common chief complaint, resulting in approximately 7 million physician office visits per year in the US. Fatigue is a non-specific symptom which can be associated with many acute or chronic conditions. In our clinical experience fatigue is a frequent reason for referral to the endocrine clinic, and often assessment does not reveal an endocrine pathology. However, the prevalence of endocrinopathies discovered following endocrinology assessment has not been well studied. Methods: In this retrospective study, we completed chart review of electronic medical records of patients who were evaluated for a chief complaint of fatigue at outpatient endocrinology centers belonging to an integrated health network in the Pittsburgh Metro area. We included patients aged 18-40 years old from 01/01/2019- 12/31/2022. We hypothesized that there is not a significant incidence of endocrinopathies found on evaluation. Results: Extensive clinical and laboratory data were gathered for 226 patients during the study period. 39.9% of patients were self-referred. 60.1% of patients seen were through physician referrals, however 17.9% of these patients had no prior investigations completed. The majority of patients evaluated for fatigue were female (76.5% vs 23.5%). 55.3% of patients were 30-39 years of age. 27% of patients were overweight and 23% were obese with BMI 30 or greater. Nearly half of all patients had a diagnosis of anxiety or depression (51.7% and 48.2% respectively). Of those patients with anxiety, 57.3% were prescribed an SSRI or SNRI. Similarly, 58.7% of patients with depression were prescribed an SSRI/SNRI. Patients most commonly reported other non-specific symptoms such as weight gain, poor sleep and poor mood (51.3%, 38.9%, 25.2% respectively). 54.9% of female patients presenting with fatigue were concerned for thyroid dysfunction whereas 45.3% of male patients were concerned for hypogonadism. 12.3% of patients evaluated never completed the recommended testing. Vitamin D deficiency was notably prevalent in 42.4% of patients tested. One patient was found to have secondary adrenal insufficiency in the setting of chronic exogenous glucocorticoid use for back pain. Of 163 patients tested for thyroid dysfunction, no new diagnoses of thyroid abnormalities were revealed. Conclusion: In this study, laboratory testing from an endocrinology consultation was not useful in detecting newly discovered endocrinopathies as a cause of fatigue. Presentation: 6/2/2024

Osteoporosis in older men

Osteoporosis, characterized by reduced bone mass and compromised skeletal microarchitecture, significantly increases the risk of fractures and is the most prevalent metabolic bone disease. While it is commonly associated with post-menopausal women, osteoporosis and subsequent fractures are also substantial concerns in men. Men experience sustained bone loss after the sixth decade, with estimates indicating that 20% of Americans with osteopenia or osteoporosis are men. Approximately one in eight men over 50 will suffer an osteoporotic fracture, with hip fractures in men leading to a two- to threefold increase in mortality compared to women. The prevalence of osteoporosis in men has risen, doubling in prevalence since the early 1990s. Men generally have higher peak bone mass and greater bone size, offering some protection against osteoporosis; however, aging leads to increased bone resorption and decreased bone formation, exacerbated by lower androgen and estrogen levels. Secondary causes, such as hypogonadism and chronic glucocorticoid use, are prevalent in men. Diagnosis primarily involves bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA), with fracture risk assessment tools like FRAX and MORES aiding in clinical decisions. Treatment includes calcium and vitamin D supplementation, bisphosphonates, denosumab, and anabolic agents like teriparatide and abaloparatide. Special considerations are necessary for men undergoing androgen deprivation therapy for prostate cancer due to accelerated bone loss. Effective management requires early diagnosis, lifestyle modifications, and appropriate pharmacological interventions to reduce fracture risk and improve patient outcomes.

Truth unveiled by time and the marbled definition of D2T-RA: retrospective analysis on the persistence of the difficult-to-treat status among refractory RA patients

BackgroundThe current EULAR definition of difficult-to-treat rheumatoid arthritis (D2T-RA) identifies patients with active disease refractory to multiple treatments at a single time point, without considering the persistence of this condition over time. The study aimed to assess difficult-to-treat rheumatoid arthritis (D2T-RA) over 12 months, considering persistence over time rather than a single time point, in a real-life cohort.MethodsIn a single-center real-life cohort, demographic and clinic data were cross-sectionally collected for each patient at baseline and retrospectively over the previous 12 months bimonthly. For each timepoint, the prevalence of D2T-RA patients was calculated, and patients meeting the EULAR definition for at least 6 months were defined as persistent D2T-RA (pD2T-RA). Finally, the clinical characteristics associated with the time-based definition of pD2T-RA were analyzed.ResultsAmong 610 adult RA patients, 104 were refractory to ≥ 2 treatments. Initially, 41.3% met D2T-RA criteria, but only 27.9% fulfilled persistent D2T-RA (pD2T-RA) criteria over 6 months. The pD2T-RA group was associated with male gender, higher HAQ and Charlson Comorbidity Index scores, more failed treatments, and use of non-NSAID analgesics. Logistic regression linked pD2T-RA to higher SDAI and CRP values, and the use of glucocorticoids or analgesics. Chronic use of glucocorticoids was strongly associated with pD2T-RA.ConclusionsThe application of a temporal criterion allowed for the selection of a subgroup of pD2T-RA patients who differ from those who meet the definition of D2T-RA only episodically. Chronic use of glucocorticoids was the factor most strongly associated with pD2T-RA status.

Rheumatology: What You May Have Missed in 2023.

Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published in 2023 that offer valuable insights for internal medicine specialists and subspecialists outside of rheumatology. The first study investigated the effect of low-dose glucocorticoids on patients with rheumatoid arthritis (RA) over 2 years and challenged existing perceptions about the risks of glucocorticoids in this setting. The second study focused on the updated guideline for preventing and treating glucocorticoid-induced osteoporosis. With the chronic and widespread use of glucocorticoids, the American College of Rheumatology emphasized the importance of assessing fracture risk and initiating pharmacologic therapy when appropriate. The third study explored the potential use of methotrexate in treating inflammatory hand osteoarthritis, suggesting a novel approach to managing this challenging and common condition. The results of the fourth article we highlight suggest that sarilumab has promise as an adjunct treatment of polymyalgia rheumatica relapse during glucocorticoid dosage tapering. The fifth study evaluated sublingual cyclobenzaprine for fibromyalgia treatment, noting both potential benefits and risks. Finally, the sixth article is a systematic review and meta-analysis that assessed the therapeutic equivalence of biosimilars and reference biologics in the treatment of patients with RA. Knowledge of this recent literature will be useful to clinicians regardless of specialty who care for patients with these commonly encountered conditions.

Channel Expansion in the Ligand-Binding Domain of the Glucocorticoid Receptor Contributes to the Activity of Highly Potent Glucocorticoid Analogues.

Glucocorticoids (GCs) act through the glucocorticoid receptor (GR) and are commonly used as anti-inflammatory and immunosuppressant medications. Chronic GC use has been linked with unwanted complications such as steroid-induced diabetes mellitus (SIDM), although the mechanisms for these effects are not completely understood. Modification of six GC parent molecules with 2-mercaptobenzothiazole resulted in consistently less promoter activity in transcriptional activation assays using a 3xGRE reporter construct while constantly reducing inflammatory pathway activity. The most selective candidate, DX1, demonstrated a significant reduction (87%) in transactivation compared to commercially available dexamethasone. DX1 also maintained 90% of the anti-inflammatory potential of dexamethasone while simultaneously displaying a reduced toxicity profile. Additionally, two novel and highly potent compounds, DX4 and PN4, were developed and shown to elicit similar mRNA expression at attomolar concentrations that dexamethasone exhibits at nanomolar dosages. To further explain these results, Molecular Dynamic (MD) simulations were performed to examine structural changes in the ligand-binding domain of the glucocorticoid receptor in response to docking with the top ligands. Differing interactions with the transcriptional activation function 2 (AF-2) region of the GR may be responsible for lower transactivation capacity in DX1. DX4 and PN4 lose contact with Arg611 due to a key interaction changing from a stronger hydrophilic to a weaker hydrophobic one, which leads to the formation of an unoccupied channel at the location of the deacylcortivazol (DAC)-expanded binding pocket. These findings provide insights into the structure-function relationships important for regulating anti-inflammatory activity, which has implications for clinical utility.

Current Practice, Trends and Attitudes of Rheumatologists Towards Glucocorticoids Use for Rheumatoid Arthritis (GURANTEE): A National Cross-sectional Survey Across China

Background: There were mixed practices and attitude towards glucocorticoids (GC) use for rheumatoid arthritis (RA). We aimed to investigate current practices, changes, and perceptions of rheumatologists regarding GC use in RA patients. Methods: A cross-sectional survey was conducted using a structured questionnaire between April and August 2023. Rheumatologists from 31 province-level regions of Mainland China were invited to participate. Chi-squared tests were adopted to investigate the differences by sociodemographic characteristics. Results: 1,717 rheumatologists from 598 hospitals completed the survey with a response rate of 92%. Up to 60% of participants expressed currently infrequent initiation of GC co-therapy with csDMARDs (hardly ever 7.0%; occasionally 24.6%; sometimes 29.1%), accompanied by a decline of frequency over time reported in 64.2%. Regarding attitudes towards bridging therapy with GC, 604 (35.2%) participants supported this approach, 468 (27.3%) opposed it, and 645 (37.6%) remained inconclusive. Time to GC discontinuation in context of csDMARDs was commonly reported within 6 months in current practice which has been narrowed over time. Reasons for chronic GC use were mostly reported due to suboptimal disease control, followed by the need of RA complications, and pre-existing comorbidities. After failure of GC cessation, majority of respondents (84.4%) would escalate RA therapy (commonly by addition of JAK inhibitors, TNF inhibitors), which usually or often facilitated the GC cessation. The most frequently reported advantages and weaknesses of GC were rapid and strong efficacy, adverse events, respectively. Regarding long-term low-dose GC use for RA, the percentage of respondents who supported, opposed, or depended on the situation were 15.9%, 17.2%, and 66.9%, respectively. Conclusion: The current data demonstrate that GC initiation for RA treatment is not as frequent as before and the awareness of GC discontinuation is growing in current practice. Attitudes towards GC co-therapy with csDMARDs vary considerably and long-term low-dose GC use remain situation dependent.

Advancements in Bullous Pemphigoid Treatment: A Comprehensive Pipeline Update.

Bullous pemphigoid (BP) is a common autoimmune bullous disease affecting mainly the elderly, with rising incidence due to increased life expectancy. This disease is characterized by tense bullous lesions on normal or erythematous skin, accompanied by pruritus. BP pathogenesis involves autoantibodies against hemidesmosomal proteins BP180 and BP230, leading to detachment at the dermo-epidermal junction as well as blister formation. BP is associated with coexisting comorbidities and drug exposure, and its management often requires high doses or chronic use of systemic glucocorticoids, posing risks of adverse effects. This review focuses on novel treatment options for BP, exploring therapies targeting different immune pathways. Rituximab, a CD20 monoclonal antibody, depletes B-lymphocytes and has shown efficacy in severe cases. Dupilumab, targeting interleukin (IL)-4 receptor α and thus blocking IL-4 and IL-13, downregulates type 2 helper (Th2) responses and has demonstrated promising results. Targeting eosinophil-related molecules using bertilimumab and AKST4290 has yielded positive results in clinical trials. Omalizumab, an immunoglobulin (Ig)E antibody, can reduce disease severity and allows corticosteroid tapering in a number of cases. Complement inhibitors such as nomacopan and avdoralimab are being investigated. IL-17 and IL-23 inhibitors such as secukinumab and tildrakizumab have shown potential in a limited number of case reports. Neonatal Fc receptor antagonists such as efgartigimod are under investigation. Additionally, topical therapies and Janus kinase inhibitors are being explored as potential treatments for BP. These novel therapies offer promising alternatives for managing BP, with potential to improve outcomes and reduce high cumulative doses of systemic corticosteroids and related toxicities. Further research, including controlled clinical trials, is needed to establish their efficacy, safety, and optimal dosing regimens for BP management.

A risk of serious anaphylatic reactions to asthma biologics: a pharmacovigilance study based on a global real-world database

Asthma is a chronic inflammatory condition that affects the lung airways. Chronic use of oral glucocorticoids in patients with severe asthma is associated with several adverse events (AEs). Biologics (omalizumab, benralizumab, mepolizumab, reslizumab, and dupilumab) have been developed as alternative therapies for the treatment of asthma. In this study, we aimed to evaluate the risk of anaphylactic reactions associated with these five biologics based on a large global database. We utilized individual case reports from the Uppsala Monitoring Center from January 1968 to December 29, 2019. A disproportionality analysis was performed over all drugs and monoclonal antibodies. Anaphylactic reactions were defined according to the "anaphylactic reaction” of the standardized MedDRA queries. Contrary to dupilumab, omalizumab, benralizumab, and mepolizumab demonstrated positive signals related to anaphylactic reactions over all drugs and monoclonal antibodies. Reslizumab, which represented only 315 cases of all AEs, requires more reports to determine its association with anaphylactic reactions. More anaphylactic reactions have been identified than are known, and most cases (96.2%) are reported to be serious. Our findings indicate that omalizumab, benralizumab, and mepolizumab for asthma treatment are associated with a high risk of anaphylactic reactions; thus, more careful monitoring in the post-administration period is recommended.

Efficacy/Safety of the Use of Glucocorticoids in Oral and Maxillofacial Surgery.

Glucocorticoids, also known as corticosteroids or steroids, are drugs derived from cholesterol. They are synthesized by the adrenal cortex, along with other hormones, such as cortisol and aldosterone. Glucocorticoids are drugs recommended for patients undergoing surgery on the oral cavity, facial skeleton, and related cervical structures due to their high efficacy against inflammatory and immune processes. However, these drugs are restricted due to their multiple and serious adverse effects. The objective of this study was to verify the efficacy of corticosteroids administered in major surgeries of the oral cavity, as well as of the cervical and facial structures, based on the characteristics of the patient so as to select the best therapeutic strategy. Articles in the databases of PubMed, Nature Portfolio, Medline, Cochrane Library, and Google Scholar were thoroughly examined. A total of 54 articles were selected to address the proposed objectives. The results obtained show that it is effective and safe to use glucocorticoids as pre- or postsurgical therapy in oral and maxillofacial surgery to control the processes of inflammation, pain, lockjaw, and edema. However, when referring to the use of these drugs, one must proceed with caution and pay particular attention when handling them. The concentration of the glucocorticoids used must be individualized, as well as the selection of the route of administration. Various studies show that, although the oral route is the most used route, the most effective route is the intramuscular route due to its easy absorption. However, for patients who have recurrent inflammatory and vesiculobullous ulcerative lesions, the topical route should be chosen to mitigate side effects, considering that recurrent applications must be made to prevent the worsening of the lesion and to avoid having to use medications enterally. In patients with cervicofacial infections, antibiotics continue to be the main drugs used to manage the condition in conjunction with corticosteroids. It is important to know the possible interactions of glucocorticoids with other medicines or food: it has been described that the interaction between Ritonavir, an antiretroviral drug that inhibits human immunodeficiency virus (HIV) proteases, and prednisone causes an increase in the concentration of prednisone, leading to possible toxicity in normally safe doses and, in many cases, iatrogenic Cushing's syndrome. It is also important to know the systemic or topical adverse effects of the chronic or high-dose use of glucocorticoids. It can be concluded that by making adequate use of glucocorticoid therapy in oral and maxillofacial surgery to manage clinical manifestations, it is possible to attenuate the morbidities of treatment and intervention.

FRI233 Adrenal Insufficiency Due To An Unusual Culprit

Abstract Disclosure: S. Decamps: None. K.T. Yeung: None. K. McCowen: None. Background: Chronic exogenous use of glucocorticoids is the most common cause of reversible secondary adrenal insufficiency (AI). There is a significant risk of cortisol deficiency if the medication is abruptly discontinued. Chronic glucocorticoid therapy may cause hypothalamic-pituitary-adrenal (HPA) axis suppression, resulting in low ACTH, atrophy of the adrenal zona fasciculata and decreased cortisol production. Immunotherapy rarely causes reversible central AI, usually permanent. We present a case of an immunotherapy-receiving patient who presented with biochemical evidence of adrenal insufficiency after using an oral solution (swish and spit) of dexamethasone as prophylaxis for mucositis. Patient Summary: A 52-year-old woman with stage IIb triple negative breast cancer receiving neoadjuvant Datopotamab, Dertuxtecan and Durvalumab was evaluated for adrenal insufficiency. Prior to starting therapy, serum cortisol level measured 7.9 mcg/dL at 11 AM (normal 6.0-18.4 mcg/dL at 6-10 A.M). She had received a single dose of dexamethasone 10 mg IV with her first cycle, but not thereafter. As part of the immunotherapy protocol, serial cortisol levels were obtained, and 2 weeks after the baseline, noon serum cortisol was 1.0 ug/dL. Patient was asymptomatic. At no point were glucocorticoids replaced, but 1-week later serum cortisol level was 0.6ug/dL at 11:00 AM along with an ACTH of 5 pg/mL. Immunotherapy-induced AI was strongly suspected. Her only glucocorticoid exposure had been a dexamethasone oral mouth rinse (swish 10mL for 1 minute and spit out, four times daily). Cortisol level at 7AM a week later measured 3.5 mcg/dL with ACTH 18.7 pg/mL and a dexamethasone level 108.2 ng/dL (normal < 50 ng/dL for patients not on dexamethasone). Technique of swish and spit was reviewed with the patient, and she was not ingesting the medication. An observational approach was pursued at this time given hemodynamic stability, treatment was continued and several weeks later repeat labs showed cortisol levels of 3.3 (7AM), with a dexamethasone level of 84.3 ng/dL. Her course of therapy has been completed, so she has been off the dexamethasone solution, continues to be asymptomatic and repeat labs now show a 9AM Cortisol level of 9.5 mcg/dL and, given lack of other sources, it is most likely that these low cortisol levels along with elevated dexamethasone levels are related to the use of dexamethasone swish and spit rather than immunotherapy induced permanent HPA axis suppression. Conclusion: There is no literature on dexamethasone swish and spit being absorbed systemically possibly leading to potentially reversible HPA suppression. Our case will raise awareness of help guide clinicians expand their differential when working up these patients. Presentation: Friday, June 16, 2023

FRI326 Hypophysitis: A Formidable Diagnostic Challenge

Abstract Disclosure: S. Pandey: None. C. Houston: None. Background: Hypophysitis, defined as inflammation of the pituitary gland, may pose a formidable diagnostic challenge due to its protean clinical manifestations and growing spectrum of potential causes. We present a case of a young man with presumed hypophysitis in whom the etiology remains unknown. Case Summary: A previously healthy 20-year-old male with bilateral gynecomastia was referred to the endocrinology clinic. He reported a 1-year history of worsening fatigue, weight gain, intermittent headaches, bilateral breast enlargement, lack of morning erections, polydipsia, and polyuria. His childhood growth and pubertal development were reportedly normal. He denied prior head or testicular trauma, major systemic illnesses, and chronic opiate or glucocorticoid use. His physical exam was remarkable only for scant facial hair and bilateral nontender gynecomastia. His visual fields were normal, and sense of smell was intact. Laboratory evaluation at 8am revealed low total and free testosterone of 32 ng/dL (240-950) and 0.98 ng/dL (5.25-20.7), respectively, with LH of 1.4 mIU/mL (1.0-12.0) and FSH of 1.9 mIU/mL (1.0-12.0). Free T4, prolactin, IGF-1, and serum sodium were all within normal ranges. Serum cortisol was modestly elevated at 22.3 ug/dL (3.7-19.4) with normal ACTH of 49 pg/mL (7.2-63.0). Pituitary MRI showed diffuse thickening and enhancement of the pituitary stalk, compatible with infundibular hypophysitis, without evidence of mass effect upon the native gland or surrounding structures. Additional testing showed normal levels of serum calcium, iron, ferritin, ESR, and antinuclear antibodies. After overnight water deprivation, his serum sodium was elevated at 156 mmol/L (134-144) with low urine osmolality of 121 mOsmol/kg (300-900). He was started on desmopressin and testosterone, and close clinical monitoring was enacted. Conclusion: The diagnosis of hypophysitis poses multiple challenges. Its clinical manifestations can vary widely, including symptoms related to mass effect and/or symptoms of pituitary dysfunction. Diagnosis is often presumptive based on history and exam, biochemical evaluation, and neuroimaging. The spectrum of potential causes is broad and growing, including infiltrative, infectious, neoplastic, immunoglobulin G4-related, immunotherapy-induced, other autoimmune, and paraneoplastic causes. It is often a humbling experience for clinicians to narrow this exhaustive differential. Pituitary biopsy is the gold standard for diagnosis but poses significant risks, so is reserved for cases when the diagnosis remains uncertain or malignancy is suspected. Close clinical monitoring and re-evaluation is an acceptable alternative in select cases. Presentation: Friday, June 16, 2023

Chronic Glucocorticoid Use and Risk for Advanced Prostate Cancer at Presentation: A SEER-Medicare Cohort Study

BackgroundExamine the relationship between exposure to systemic glucocorticoids (steroids) and advanced prostate cancer (PCa) at presentation. Prior work suggested that steroid use may be associated with increased PCa risk. Materials and MethodsWe queried the linked SEER-Medicare database (2004-2015) to identify PSA screened patients diagnosed with PCa. Criteria for screening included a PSA lab test or DRE exam in both the 12 month and 13 to 36 month periods prior to diagnosis of PCa. Steroid exposure was determined using Medicare Part D and groups were divided based on duration of use in the 3 years prior to diagnosis: controls with no exposure, <30 days, 30 days – 1 year, 1 to 2 years, and >2+ years. Advanced PCa was defined as systemic metastases or regional lymph node metastasis at presentation. Risk estimates for advanced PCa at presentation for steroid exposure groups vs. controls were assessed with univariable and multivariable logistic regression models. ResultsWe identified 22,920 PSA screened patients diagnosed with PCa of which 29% used glucocorticoids in the exposure period. The mean (SD) duration for glucocorticoid use (in days) among all steroid users was 76.7 days (192.1). On univariable and multivariable analyses, > 2 years of steroid exposure was associated with significantly increased risk for advanced PCa (OR 2.06, 95% CI 1.35-3.14 and OR 1.74, 95% CI 1.12-2.69, respectively). ConclusionIn this population-based PSA-screened cohort, prolonged steroid use was associated with increased risk of advanced PCa at diagnosis. With the widespread use of glucocorticoids, it is important to consider the role steroids may play in PCa pathogenesis.

Oxylipin-PPARγ-initiated adipocyte senescence propagates secondary senescence in the bone marrow

The chronic use of glucocorticoids decreases bone mass and quality and increases bone-marrow adiposity, but the underlying mechanisms remain unclear. Here, we show that bone-marrow adipocyte (BMAd) lineage cells in adult mice undergo rapid cellular senescence upon glucocorticoid treatment. The senescent BMAds acquire a senescence-associated secretory phenotype, which spreads senescence in bone and bone marrow. Mechanistically, glucocorticoids increase the synthesis of oxylipins, such as 15d-PGJ2, for peroxisome proliferator-activated receptor gamma (PPARγ) activation. PPARγ stimulates the expression of key senescence genes and also promotes oxylipin synthesis in BMAds, forming a positive feedback loop. Transplanting senescent BMAds into the bone marrow of healthy mice is sufficient to induce the secondary spread of senescent cells and bone-loss phenotypes, whereas transplanting BMAds harboring a p16INK4a deletion did not show such effects. Thus, glucocorticoid treatment induces a lipid metabolic circuit that robustly triggers the senescence of BMAd lineage cells that, in turn, act as the mediators of glucocorticoid-induced bone deterioration.

Chronic Glucocorticoid Use is a Potential Risk Factor for Delayed Pancreatic Fistula after Laparoscopic Distal Pancreatectomy: A Retrospective Analysis.

Pancreatic fistula is a potentially morbid complication after distal pancreatectomy. Chronic glucocorticoid use is one of the risk factors for pancreatic fistula in pancreaticoduodenectomy, though it has not been reported in distal pancreatectomy. We explored whether chronic glucocorticoid use can be a risk factor for pancreatic fistula in distal pancreatectomy. We reviewed 408 consecutive patients who underwent elective distal pancreatectomy from 2011 to 2021. We evaluated two kinds of pancreatic fistula (postoperative pancreatic fistula and delayed pancreatic fistula). We defined delayed pancreatic fistula as a patient who was re-admitted for pancreatic fistula after the first discharge from the hospital. Preoperative characteristics and postoperative outcomes were analyzed. Two hundred sixty-seven patients underwent open distal pancreatectomy, while 141 patients had laparoscopic distal pancreatectomy. A comparison of patient with and without chronic glucocorticoid use showed that only patients with chronic glucocorticoid use developed delayed pancreatic fistula (0% vs. 16.7%; p < 0.001). In addition, delayed pancreatic fistula occurred in only laparoscopic distal pancreatectomy patients with chronic glucocorticoid use (0% vs. 25.0%; p < 0.001). Although sample size is small, it is reasonable to presume that chronic glucocorticoid use is a potential risk factor for delayed pancreatic fistula in laparoscopic distal pancreatectomy.

OR01-6 Bone Health Outcomes Post-Lung Transplantation in Cystic Fibrosis Patients

Abstract Background Osteoporosis is a common comorbidity in patients with cystic fibrosis (CF); malabsorption, chronic glucocorticoid use, and chronic inflammation all contribute to increased bone resorption and decreased bone formation. Although lung transplantation (LTx) improves quality of life and short- and long-term outcomes of CF patients, there is little research examining long-term bone health outcomes following LTx in these patients. Methods We collected demographic and clinical data on patients who underwent LTx at a single institution between 2006-2019 and had bone mineral density (BMD) measured pre- and post-transplantation. We compared baseline characteristics, long-term BMD trends, and fracture incidence between the two patient populations. We also examined factors associated with post-LTx fractures in CF patients. Results Charts of 59 LTx recipients were reviewed including 30 with CF and 29 without CF. Compared with non-CF patients, patients with CF were significantly younger (32.8±10.0 vs. 56.7±10.7 years), had lower body mass index (19.7±3.0 vs. 26.7±4.4 kg/m2), and significantly lower baseline BMD Z-scores at the lumbar spine (-2.0±1.1 vs. -0.3±1.6), femoral neck (-1.6±0.8 vs. -0.7±1.0), and total hip (-1.6±0.8 vs. -0.7±1.0) (all p&amp;lt;0.001). BMD at all three sites declined significantly in both groups in the first year post-LTx. In subsequent years, and compared with non-CF patients, CF patients exhibited better BMD recovery relative to pre-transplantation, but continued to have lower BMD post-LTx. Post-transplant fractures were relatively common, occurring in 30% and 34% of CF and non-CF patients, respectively. Within the CF group, those who developed fractures after LTx were more likely to have lower baseline BMD T-scores at the femoral neck (p=0.017) and total hip (p=0.050), and lower pre-transplantation percent predicted forced expiratory volume in 1 second (FEV1%) (p=0.042). Conclusions Compared with their non-CF counterparts, CF patients undergoing lung transplantation start with significantly lower BMD pre-LTx but exhibit better BMD recovery post-LTx. Despite their younger age at transplantation, CF patients experience a similarly high rate of post-LTx fractures. In CF patients, lower BMD and worse FEV1% pre-LTx are associated with development of post-LTx fractures. These findings highlight the unique contribution of the CF disease process to bone health, as well as a clear need for better prevention and treatment of osteoporosis in CF patients before and after LTx. Presentation: Saturday, June 11, 2022 12:45 p.m. - 1:00 p.m.

Exploring the Therapeutic Potential of Ectoine in Duchenne Muscular Dystrophy: Comparison with Taurine, a Supplement with Known Beneficial Effects in the mdx Mouse.

Duchenne Muscular Dystrophy (DMD) is a debilitating muscle disorder that condemns patients to year-long dependency on glucocorticoids. Chronic glucocorticoid use elicits many unfavourable side-effects without offering satisfying clinical improvement, thus, the search for alternative treatments to alleviate muscle inflammation persists. Taurine, an osmolyte with anti-inflammatory effects, mitigated pathological features in the mdx mouse model for DMD but interfered with murine development. In this study, ectoine is evaluated as an alternative for taurine in vitro in CCL-136 cells and in vivo in the mdx mouse. Pre-treating CCL-136 cells with 0.1 mM taurine and 0.1 mM ectoine prior to exposure with 300 U/mL IFN-γ and 20 ng/mL IL-1β partially attenuated cell death, whilst 100 mM taurine reduced MHC-I protein levels. In vivo, histopathological features of the tibialis anterior in mdx mice were mitigated by ectoine, but not by taurine. Osmolyte treatment significantly reduced mRNA levels of inflammatory disease biomarkers, respectively, CCL2 and SPP1 in ectoine-treated mdx mice, and CCL2, HSPA1A, TNF-α and IL-1β in taurine-treated mdx mice. Functional performance was not improved by osmolyte treatment. Furthermore, ectoine-treated mdx mice exhibited reduced body weight. Our results confirmed beneficial effects of taurine in mdx mice and, for the first time, demonstrated similar and differential effects of ectoine.

Use of Dupilumab in Glucocorticoid-Dependent Asthma

Of the patients with asthma, 20% to 25% progress to severe symptoms, resulting in poor quality of life and increased episodes of exacerbation. There is a broad range of drugs used for asthma; the most used medications for severe asthma are inhaled glucocorticoids with or without long-acting β-agonists. Systemic glucocorticoids and other treatments as add-on therapies are also given as needed. Chronic glucocorticoid use is associated with numerous adverse effects, including diabetes mellitus, osteoporosis, anxiety, depression, and cataracts. The occurrence of these side effects has been reduced because of the emergence of new biological therapies. One such treatment is dupilumab, which helps in the reduction of type 2 inflammation involved in the pathophysiology of asthma. We conducted a literature review to assess the efficacy, adverse effects, and pharmacological benefits of dupilumab in glucocorticoid-dependent asthma. In most randomized controlled trials, dupilumab has shown significant efficacy and safety profile in patients with severe asthma with corticosteroid dependence. Associated adverse effects such as injection site reaction and transient eosinophilia have been reported. Our review of the literature indicates that dupilumab has proven to improve lung function, reduce the rate of asthma exacerbations, and reduce the use of corticosteroids.

Associations of Prior Chronic Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Glucocorticoids With Cachexia Incidence and Survival.

BackgroundCachexia is an inflammatory and metabolic syndrome of unintentional weight loss through depletion of muscle and adipose tissue. There is limited knowledge of how chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids affect cachexia development. The purpose of this study was to investigate associations between prior long-term use of NSAIDs or glucocorticoids with cachexia incidence and post-diagnosis weight loss progression in a retrospective cancer patient cohort.MethodsOf 3,802 lung or gastrointestinal cancer patient records, 3,180 comprised our final cohort. Patient demographic information, tumor qualities, medication histories, and comorbidities were assessed. Cachexia was defined as having developed prior to oncologic treatment. Statistical evaluations included categorical, multivariate logistic regression, and log-rank survival analyses. Development of substantial post-diagnosis weight loss was calculated and interpreted for patients without cachexia at diagnosis.ResultsChronic prior use of any NSAID or glucocorticoid medication was associated with approximate absolute and relative reductions in cachexia incidence at diagnosis of 10 and 25 percent (P<0.0001). In multivariate analyses, NSAID medications demonstrated a 23 percent reduction in cachexia incidence likelihood (OR=0.770; 95% CI=0.594, 0.998; P=0.0481). Patients without cachexia at diagnosis were significantly more likely to develop substantial post-diagnosis weight loss from pre-diagnosis use groups of glucocorticoids (OR= 1.452; 95% CI=1.065, 1.979; P=0.0183) or NSAIDs (OR=1.411; 95% CI=1.082, 1.840; P=0.011).ConclusionsOur findings suggest a protective effect of prior anti-inflammatory medications, primarily NSAIDs, against manifestations of the cachexia phenotype at cancer diagnosis. These observations support further exploration of potential therapeutic benefits from anti-inflammatory medications early in cancer management.